Studies are being performed to evaluate mechanisms whereby articular inflammation, cartilage degradation and modulation of cartilage physiologic function are induced or perpetuated in diverse human arthridities and in experimental animal models of chondrolysis. Humoral and cell mediated immunologic reactivity to sequestered and degradative constituents of cartilage are being studied and the pathophysiologic significance of such sensitization evaluated. The role of such antibodies, lymphokines and other cytokines derived from macrophages, explants of synovial membrane, propagated synoviocytes and mast cells are being investigated as to their capacity to: (1) induce exogenous proteoglycan degradation, (2) modulate the quality and quantity of chondrocyte proteoglycan, glycosaminoglycan, protein, collagen and nucleic acid synthesis, (3) induce endogenous cartilage proteoglycan and collagen degradation by the activation and release of chondrocyte proteinases, (4) modulate lysosomal proteinase mediated cartilage proteoglycan degradation, (5) alter chondrocyte metabolic activity as assessed by phagocytosis, glucose oxidation, amino aicd and nucleoside transport and the production of superoxide anion and chemotactic factors, (6) alter proteoglycan macromolecular aggregation and (7) modulate synoviocyte function as assessed by glycosaminoglycan, protein and nucleic acid synthesis, glucose oxidation and lactate production. Further studies are evaluating the effect of proteoglycan constituent fractions on synoviocyte and chondrocyte metabolic activity and macrophage, PMN and lymphocyte afferent and efferent function.